Structure and Function of the Human Kidney

Overview: Why the Kidney Is Special

The human kidney is more than a “filter.” Each kidney is a highly organized organ that:

• Cleans the blood of waste products
• Regulates water and salt balance
• Helps keep blood pH and blood pressure stable
• Produces hormones

This chapter focuses on its structure and how that structure enables its functions. The detailed steps of urine formation in the nephron are covered in the next chapter.

Gross Anatomy of the Human Kidney

Location and External Structure

• Humans typically have two kidneys, located in the upper posterior abdomen, on either side of the spine, behind the peritoneum (they are retroperitoneal).
• They lie roughly between the levels of the lower thoracic and upper lumbar vertebrae.
• Right kidney is usually slightly lower than the left because of the liver.

Each kidney has:

• Bean-shaped form
• Size: about 10–12 cm long, 5–7 cm wide, 3–4 cm thick (adult)
• Outer convex border and inner concave border

On the inner concave border is the:

• Renal hilum (or hilus): a slit-like opening where major structures enter and leave:
• Renal artery (blood in)
• Renal vein (blood out)
• Ureter (urine out)
• Lymph vessels and nerves

The kidney is surrounded by:

• Fibrous renal capsule: a thin, strong connective tissue layer directly on the kidney surface, protecting it and maintaining shape.
• Perirenal fat: fat cushion around the capsule for protection and fixation.
• Renal fascia: connective tissue that anchors the kidney in place.

Internal Structure: Cortex, Medulla, Pelvis

On a longitudinal section, you can distinguish three main regions:

1. Renal cortex
• Outer, lighter-colored area.
• Contains most of the renal corpuscles (glomeruli + Bowman’s capsule) and parts of the tubules.
• Granular appearance due to many tiny filtration units.
2. Renal medulla
• Inner, darker, striated region.
• Organized into pyramids:
• Renal pyramids: cone-shaped structures.
• The base of each pyramid faces the cortex.
• The tip (papilla) points toward the center of the kidney.
• Striated appearance from parallel loops of Henle and collecting ducts.

Between pyramids are:

• Renal columns (columns of Bertin): cortical tissue projecting inward between pyramids; contain blood vessels and connective tissue.

3. Renal pelvis and calyces
• The renal papillae of each pyramid protrude into small cavities:
• Minor calyces: collect urine dripping from papillae.
• Several minor calyces merge and form:
• Major calyces.
• Major calyces unite to form the renal pelvis:
• A funnel-shaped collecting space that narrows to become the ureter.

Functionally, this arrangement channels urine from microscopic structures (nephrons) through collecting ducts → papillae → calyces → pelvis → ureter.

Blood Supply of the Kidney

Renal Artery and Its Branches

The kidneys receive an unusually large portion of cardiac output (about 20–25%) to filter the blood effectively.

Path of blood flow (simplified):

• Abdominal aorta →
• Renal artery →
• Segmental arteries →
• Interlobar arteries: run between pyramids through renal columns →
• Arcuate arteries: arch along the border between cortex and medulla →
• Interlobular (cortical radiate) arteries: radiate into cortex →
• Afferent arterioles: each supplies a single glomerulus.

Within the kidney, this branching produces a very fine capillary network adapted for filtration and exchange.

Special Feature: Two Capillary Beds in Series

A distinctive aspect of renal circulation is that each nephron is associated with two capillary beds in series:

1. Glomerular capillaries
• Fed by an afferent arteriole and drained by an efferent arteriole (not a vein).
• High pressure; specialized for filtration of plasma into Bowman’s capsule.
2. Peritubular capillaries and vasa recta
• Arise from the efferent arteriole.
• Peritubular capillaries: around cortical parts of the nephron; low pressure; adapted for reabsorption and secretion.
• Vasa recta: long, hairpin-shaped capillaries running parallel to loops of Henle in juxtamedullary nephrons; important for maintaining medullary osmotic gradient.

Blood then drains into:

• Interlobular veins →
• Arcuate veins →
• Interlobar veins →
• Renal vein →
• Inferior vena cava

This precise arrangement of inflow and outflow is crucial for controlled filtration and for concentrating or diluting urine.

The Nephron: Structural and Functional Unit

Types and General Layout

A nephron is the smallest structural unit that can perform all essential kidney functions. Each human kidney contains about 1–1.5 million nephrons.

Two main types:

1. Cortical nephrons
• Located mostly in the outer cortex.
• Shorter loops of Henle that dip only slightly into the medulla.
• Make up the majority of nephrons.
• Primarily responsible for bulk filtration and reabsorption.
2. Juxtamedullary nephrons
• Renal corpuscles near the cortex–medulla boundary.
• Very long loops of Henle extending deep into the medulla.
• Closely associated with vasa recta.
• Crucial for creating the medullary osmotic gradient and thus the ability to produce concentrated urine.

Basic segments of every nephron:

1. Renal corpuscle (in cortex)
2. Proximal tubule
3. Loop of Henle
4. Distal tubule
5. Connecting tubule → collecting duct (the collecting duct system serves many nephrons)

The detailed processes (filtration, reabsorption, secretion) are discussed in the following chapter; here we focus on structure and its functional implications.

Renal Corpuscle: Glomerulus and Bowman’s Capsule

The renal corpuscle is the site where blood plasma is initially filtered to form primary urine (glomerular filtrate).

It consists of:

1. Glomerulus
• A tuft of fenestrated capillaries supplied by the afferent arteriole and drained by the efferent arteriole.
• Surrounded by specialized cells and basement membranes forming the filtration barrier.
2. Bowman’s capsule
• A double-walled, cup-like structure wrapped around the glomerulus.
• Has two layers:
• Parietal (outer) layer: simple squamous epithelium forming the outer wall.
• Visceral (inner) layer: formed by podocytes, cells with numerous foot-like processes.

Between these layers lies the:

• Capsular (Bowman’s) space: where the filtrate collects before entering the proximal tubule.

The Filtration Barrier

The structural design of the filtration barrier allows water and small solutes to pass, but largely prevents cells and most proteins from leaving the blood.

Three main layers:

1. Fenestrated endothelium of glomerular capillaries:
• Contains pores (fenestrations) that allow free passage of water and small molecules, but not blood cells.
2. Glomerular basement membrane (GBM):
• Common basal lamina shared by endothelium and podocytes.
• Acts as a size and charge barrier; negatively charged, repels many plasma proteins.
3. Podocyte slit diaphragm:
• Podocyte foot processes (pedicels) interdigitate, leaving filtration slits bridged by a thin slit diaphragm.
• Further restricts passage by size and selectivity.

Structural outcome:

• Plasma is ultrafiltrated: water, ions, glucose, amino acids, urea, and many small molecules pass; large proteins and cells are retained.

Tubular System: Structural Segments

After filtrate enters the capsular space, it flows through the nephron’s tubules, which are structurally specialized to adjust its composition.

Proximal Tubule

Located in the cortex, divided (histologically) into:

• Proximal convoluted tubule (PCT)
• Proximal straight tubule

Main structural features:

• Cuboidal epithelial cells with:
• Dense brush border (microvilli) on the luminal side, massively increasing surface area.
• Numerous mitochondria for active transport.
• Tight but relatively leaky junctions allow coupling of water and solute movement.

Functional consequence:

• Adapted for intensive reabsorption of most filtered water and solutes, and for secretion of certain substances.

Loop of Henle

A U-shaped segment that dips into the medulla. It has:

1. Descending limb
• Starts as thick segment (from proximal straight tubule) and continues as thin descending limb.
• Thin segment has flat, squamous epithelial cells.
2. Ascending limb
• Thin ascending limb (in deeper medulla) in some nephrons.
• Thick ascending limb (TAL): returns to cortex; cuboidal cells with many mitochondria.

Functional implications of structure:

• Thin descending limb: highly permeable to water, relatively less to salts.
• Thick ascending limb: largely impermeable to water but rich in ion transporters, especially for Na⁺, K⁺, Cl⁻.
• This structural difference between limbs is crucial for forming the countercurrent system that establishes a salt gradient in the medulla.

Distal Tubule

Begins after the macula densa (see below), located in the cortex.

Structural features:

• Distal convoluted tubule (DCT): shorter and less convoluted than PCT.
• Lined by cuboidal epithelial cells:
• Fewer and shorter microvilli (no prominent brush border).
• Many mitochondria for active ion transport.
• Tighter tight junctions; epithelium is less “leaky”.

Functional consequence:

• Specialized for fine regulation of ion composition (Na⁺, K⁺, Ca²⁺, etc.) of the tubular fluid.

Collecting Duct System

While not strictly part of a single nephron, the collecting duct system is structurally continuous with the nephron and central to kidney function.

Components:

• Connecting tubules from several nephrons join to form a collecting duct.
• Collecting ducts run through cortex and medulla, fusing into larger ducts (e.g., papillary ducts) that open at the renal papilla into minor calyces.

Cell types:

1. Principal cells
• Relatively few short microvilli.
• Respond to hormones like aldosterone (Na⁺ reabsorption, K⁺ secretion) and antidiuretic hormone (ADH) (water permeability).
2. Intercalated cells
• More mitochondria.
• Important in acid–base regulation (secretion of H⁺ or HCO₃⁻).

Functional consequence:

• The collecting system is a final adjustment zone where the kidney regulates water content and some ions, largely under hormonal control.

Juxtaglomerular Apparatus: Structure and Role

At the point where the distal tubule of a nephron passes close to its own afferent and efferent arterioles, there is a specialized structure called the juxtaglomerular apparatus (JGA).

It consists of three main components:

1. Macula densa
• A group of densely packed, tall epithelial cells in the wall of the distal tubule.
• Located where the tubule contacts the glomerulus.
• Sensitive to the NaCl concentration and flow in the tubular fluid.
2. Juxtaglomerular (JG) cells
• Modified smooth muscle cells in the wall of the afferent arteriole (and to a lesser extent the efferent arteriole).
• Contain secretory granules with renin, an enzyme important in blood pressure and volume regulation.
3. Extraglomerular mesangial cells
• Cells located between the macula densa and arterioles.
• Thought to participate in signal transmission and possibly structural support.

Functional significance:

• The JGA provides local feedback between tubular fluid and the glomerular blood supply (tubuloglomerular feedback).
• It contributes to systemic regulation of blood pressure and blood volume via renin release.

Microscopic Supporting Structures

Beyond the nephron and blood vessels, several structural elements support kidney function:

Interstitium

• The interstitial tissue lies between tubules and blood vessels.
• Contains:
• Fibroblast-like cells
• Immune cells
• Interstitial matrix and extracellular fluid

In the medulla:

• Interstitial cells produce prostaglandins and other signaling molecules.
• The composition of interstitial fluid is critical for the osmotic gradient used in urine concentration.

Mesangial Cells

Found within the glomerulus and at the vascular pole.

Roles:

• Provide structural support for glomerular capillaries.
• Can contract, thereby adjusting capillary surface area available for filtration.
• Participate in phagocytosis of debris and in immune responses.
• Produce components of the extracellular matrix and signaling molecules.

Functional Tasks of the Human Kidney

The kidney’s structure is dedicated to several key tasks:

1. Excretion of Metabolic Waste and Foreign Substances

• Removal of small, water-soluble waste products from the blood, such as:
• Urea (from amino acid metabolism)
• Creatinine (from muscle metabolism)
• Uric acid
• Metabolites of drugs and toxins

Structural basis:

• High blood flow and glomerular filtration → waste enters filtrate.
• Tubular secretion from peritubular capillaries into tubules enhances elimination of certain substances.

2. Regulation of Water and Electrolyte Balance

• Maintaining overall body water and the balance of key ions (Na⁺, K⁺, Cl⁻, Ca²⁺, Mg²⁺, phosphate).

Structural basis:

• Differently specialized tubule segments with distinct transport proteins.
• Countercurrent system: loops of Henle and vasa recta create a gradient allowing the kidney to concentrate or dilute urine.
• Collecting ducts adjust final water reabsorption under ADH influence.

3. Regulation of Acid–Base Balance

• Helps keep blood pH within a narrow range by:
• Reabsorbing filtered bicarbonate (HCO₃⁻).
• Secreting hydrogen ions (H⁺) and producing new bicarbonate.

Structural basis:

• Specific transporters in proximal tubule and intercalated cells of collecting ducts.
• Large contact area between tubular fluid and blood.

4. Regulation of Blood Pressure and Blood Volume

• Adjusts extracellular fluid volume (by controlling Na⁺ and water excretion).
• When needed, influences systemic blood pressure.

Structural basis:

• Juxtaglomerular apparatus senses changes in blood pressure and NaCl.
• JG cells release renin, initiating the renin–angiotensin–aldosterone system (RAAS) (detailed elsewhere).
• Structural alignment of arterioles and macula densa allows precise feedback.

5. Endocrine and Metabolic Functions

The kidney is also an endocrine organ:

• Erythropoietin (EPO):
• Produced mainly by interstitial cells in the renal cortex and outer medulla.
• Stimulates red blood cell production in the bone marrow when oxygen supply is low.
• Activation of Vitamin D:
• Kidney converts vitamin D into its active form, calcitriol, via a hydroxylation step.
• Important for calcium and phosphate homeostasis, and bone health.
• Prostaglandins and other signaling molecules:
• Modulate blood flow and various local processes.

These endocrine roles depend on the kidney’s specialized interstitial cells, tubular epithelium, and enzymatic systems.

Structural Adaptations and Clinical Relevance (Brief)

Because structure and function are tightly linked, damage to specific kidney structures leads to characteristic problems:

• Glomerular damage (e.g., injury to the filtration barrier):
• Proteins and sometimes blood cells appear in urine (proteinuria, hematuria).
• Tubular damage:
• Impaired reabsorption or secretion.
• Problems with water, salt, or acid–base balance.
• Loss of nephrons:
• Reduced overall filtration capacity.
• Remaining nephrons may adapt, but extensive loss leads to kidney failure.

Understanding the structural organization of the human kidney—down to the level of nephrons and specialized cell types—is essential for grasping how it forms urine (covered in the next chapter) and maintains internal stability for the whole body.